John M. Galla

Comparison of percutaneous versus surgical revascularization of severe unprotected left main coronary stenosis in matched patients.

Coronary artery bypass grafting (CABG) has been the recommended treatment for patients with significant left main coronary artery (LMCA) stenosis. Advances in stent technology have invigorated investigations into the suitability of a percutaneous approach for these patients. Favorable short-term results from nonrandomized comparisons were previously reported. Patients (n = 97) who underwent percutaneous coronary intervention for severe (>70%) LMCA stenosis were matched in a 1:2 ratio with a cohort that underwent surgical revascularization (n = 190). The groups were similar for age, gender, European System for Cardiac Operative Risk Evaluation, left ventricular ejection fraction, history of myocardial infarction, and presence of renal disease. Kaplan-Meier estimates of 3-year mortality were similar for the PCI and CABG groups at 80% (95% confidence interval [CI] 68 to 88) versus 85% (95% CI 79 to 89, p = 0.14), respectively. Propensity score-adjusted 3-year mortality did not differ between groups (p = 0.22). Multivariable modeling identified only higher European System for Cardiac Operative Risk Evaluation (hazard rate 1.33, 95% CI 1.16 to 1.54, p <0.001) and the presence of diabetes mellitus (hazard rate 1.96, 95% CI 1.24 to 3.09, p = 0.004) as independent risks of mortality at 3 years. In conclusion, patients who underwent percutaneous revascularization of severe LMCA stenosis appeared to have 3-year survival equivalent to those who underwent CABG. Diabetes mellitus and advanced co-morbidity were the principal determinants of survival. These findings support the need for randomized trials with adequate follow-up to compare the 2 approaches.

Inhibition of delta-protein kinase C by delcasertib as an adjunct to primary percutaneous coronary intervention for acute anterior ST-segment elevation myocardial infarction: results of the PROTECTION AMI Randomized Controlled Trial

AIMS Delcasertib is a selective inhibitor of delta-protein kinase C (delta-PKC), which reduced infarct size during ischaemia/reperfusion in animal models and diminished myocardial necrosis and improved reperfusion in a pilot study during primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI). METHODS AND RESULTS A multicentre, double-blind trial was performed in patients presenting within 6 h and undergoing primary PCI for anterior (the primary analysis cohort, n = 1010 patients) or inferior (an exploratory cohort, capped at 166 patients) STEMI. Patients with anterior STEMI were randomized to placebo or one of three doses of delcasertib (50, 150, or 450 mg/h) by intravenous infusion initiated before PCI and continued for ∼2.5 h. There were no differences between treatment groups in the primary efficacy endpoint of infarct size measured by creatine kinase MB fraction area under the curve (AUC) (median 5156, 5043, 4419, and 5253 ng h/mL in the placebo, delcasertib 50, 150, and 450 mg/mL groups, respectively) in the anterior STEMI cohort. No treatment-related differences were seen in secondary endpoints of infarct size, electrocardiographic ST-segment recovery AUC or time to stable ST recovery, or left ventricular ejection fraction at 3 months. No differences in rates of adjudicated clinical endpoints (death, heart failure, or serious ventricular arrhythmias) were observed. CONCLUSIONS Selective inhibition of delta-PKC with intravenous infusion of delcasertib during PCI for acute STEMI in a population of patients treated according to contemporary standard of care did not reduce biomarkers of myocardial injury.

Left Main Trunk Coronary Artery Dissection as a Consequence of Inaccurate Coronary Computed Tomographic Angiography

A 52-year-old woman presented to a community hospital with atypical chest pain. Her low-density lipoprotein cholesterol and high-sensitivity C-reactive protein levels were not elevated. She underwent cardiac computed tomography angiography, which showed both calcified and noncalcified coronary plaques in several locations. Her physicians subsequently performed coronary angiography, which was complicated by dissection of the left main coronary artery, requiring emergency coronary artery bypass graft surgery. Her subsequent clinical course was complicated, but eventually she required orthotopic heart transplantation for refractory heart failure. This case illustrates the hazards of the inappropriate use of cardiac computed tomography angiography in low-risk patients and emphasizes the need for restraint in applying this new technology to the evaluation of patients with atypical chest pain.

Transient post-operative atrial fibrillation predicts short and long term adverse events following CABG

OBJECTIVE To assess the relationship between the development of transient post-operative atrial fibrillation (TPOAF) following coronary artery bypass graft (CABG) surgery and risk of long-term mortality. BACKGROUND Atrial fibrillation (AF) following CABG is common and associated with increased morbidity and mortality in the perioperative period. However the impact of TPOAF and its management on long-term morbidity and mortality in patients undergoing first time, isolated CABG surgery remains unclear. METHODS The Cleveland Clinic Cardiovascular Information Registry was used to identify 5,205 consecutive patients who underwent CABG between January 1993 and December 2005. Patients with TPOAF (n=1,490) were compared to those without post-operative AF (n=3,645) for the endpoints of death, myocardial infarction (MI), or stroke at 1 year. RESULTS Overall rates of 1-year mortality, MI and stroke were 3.7%, 0.8%, and 2.6%, respectively. Patients with TPOAF had an increased risk of death at 1 year as compared to patients without POAF (6.4% vs. 2.7%; P<0.001), but there was not an increased risk of stroke or MI. Multivariate analysis identified TPOAF as an independent predictor of death at 1 year (HR 1.89, 95% CI, 1.42-2.53; P<0.001). After propensity matching, patients who developed TPOAF experienced a significantly increased risk of death compared with those without TPOAF (HR 1.96, 95% CI, 1.34-2.86; P<0.001). CONCLUSIONS In patients undergoing first time, isolated CABG, the presence of TPOAF identifies a subgroup of patients at increased risk for all-cause mortality. Future prospective studies to determine potential beneficial interventions in this large population are warranted.

Bare metal stent thrombosis 13 years after implantation

There has been a great deal of recent controversy regarding the risk of very late stent thrombosis with drug eluting stents, especially in the context of antiplatelet therapy cessation. We report a case of very late stent thrombosis of a bare metal stent initially implanted for treatment of a myocardial infarction. The patient presented thirteen years later with a recurrent myocardial infarction three days after discontinuing aspirin. Angiography demonstrated thrombotic occlusion and severe underlying restenosis of the stent. To our knowledge, this is the latest bare metal stent thrombosis described in the world medical literature.

Coronary Chronic Total Occlusion

Chronic total coronary occlusions (CTOs) are a frequent finding in patients with coronary disease and remain one of the most challenging target lesion subsets for intervention. CTOs have been reported in approximately one-third of patients undergoing diagnostic coronary angiography. By nature of their complexity, CTO percutaneous interventions (PCIs) are associated with lower rates of procedural success, higher complication rates, greater radiation exposure, and longer procedure times compared with interventions in non-CTO stenoses. Despite these obstacles, reported benefits of successful CTO PCI include a reduction in symptoms and improvement in both ventricular function and survival. This article examines the technical challenges, procedural complications, and possible outcomes associated with CTO PCI.

Pharmacologic therapy for coronary atherosclerosis in patients with Type 2 diabetes mellitus

Accelerated progression of coronary atherosclerosis underlies the heightened cardiovascular risk observed in diabetic patients. As the worldwide prevalence of diabetes escalates in association with the incidence of abdominal obesity, the global burden of cardiovascular disease will continue to rise. Therapeutic strategies that have had the greatest cardiovascular benefit in diabetes have focused on lowering LDL-cholesterol and blood pressure, rather than glucose-lowering specifically. More recently, arterial wall imaging has helped characterize the natural history of coronary atherosclerosis in diabetes, the impact of associated risk factors and the influence of medical therapies.

Late Diagnosis of Multiple Fibroelastomas in a 41-Year-Old Woman with Hypertrophic Cardiomyopathy and Atrial Fibrillation

A 39 year old woman with hypertrophic cardiomyopathy with severe latent obstruction and mitral regurgitation, presented with symptoms of dyspnea and atrial fibrillation, and developed an acute embolic stroke. After thrombolysis and complete neurologic recovery, a transesophageal echo revealed six mobile densities, on her mitral and aortic valves, and in the outflow tract. Surgical resection of multiple fibroelastomas, with septal myectomy, aortic and mitral valve replacement, and pulmonary vein ablation, led to clinical improvement. The etiology and pathogenesis of fibroelastomas are unknown; we speculate that their formation may be promoted by endocardial injury from surgery, radiation therapy, or the high velocity turbulent flow of valve dysfunction or outflow tract obstruction.

Antithrombin Therapy for Acute ST-Segment Elevation Myocardial Infarction

Thrombus formation at the site of plaque rupture has long been recognized as the inciting event in the pathophysiology of ST-segment elevation myocardial infarction (STEMI). Fibrinolysis remains the most common mode of revascularization worldwide and has the recognized limitation of creating large amounts of activated thrombin as a byproduct of its mechanism of action. Several antithrombin agents have been developed as adjuncts to either pharmacologic or mechanical revascularization strategies for this patient population. Unfractionated heparin remains a very important agent although low-molecular weight heparins and direct thrombin inhibitors have been developed and studied in these patients. How each class of antithrombin therapies will be optimally utilized for patients with STEMI remains to be defined. At the core of any antithrombin therapy rests the goals of minimizing ischemic complications while simultaneously avoiding any bleeding complications.

Impact of statin therapy on the artery wall in the low-risk patient: implications from the METEOR study

Lowering levels of LDL-cholesterol is associated with profound clinical benefit. More recently, it has been demonstrated that intensively lowering LDL-cholesterol to very low levels is associated with greater benefit. Vascular imaging has defined that this approach has a dramatic impact on the progression of disease in the artery wall. The Measuring Effects on Intima-Media Thickness: an Evaluation of Rosuvastatin in Subclinical Atherosclerosis (METEOR) study observed that rosuvastatin halted progression of carotid intimal-medial thickness in participants with low Framingham risk scores and evidence of subclinical atherosclerosis. This extends the benefits of intensive statin therapy to patients who would not typically be treated. It also highlights the concept that imaging modalities and other emerging risk markers may identify patients who could benefit from the use of established preventive medical therapies.